18-12008848-A-G

Variant names:

• chr18-12008848-A-G
• rs3786285
• NM_014214.3:c.231-1035A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014214.3(IMPA2):​c.231-1035A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,042 control chromosomes in the GnomAD database, including 12,954 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (12954 hom., cov: 32)
• Consequence: IMPA2 NM_014214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 3 publications found

Genes affected

IMPA2 (HGNC:6051): (inositol monophosphatase 2) This locus encodes an inositol monophosphatase. The encoded protein catalyzes the dephosphoylration of inositol monophosphate and plays an important role in phosphatidylinositol signaling. This locus may be associated with susceptibility to bipolar disorder. [provided by RefSeq, Jan 2011]

ENSG00000293189 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014214.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPA2	NM_014214.3	MANE Select	c.231-1035A>G		intron	N/A	NP_055029.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPA2	ENST00000269159.8	TSL:1 MANE Select	c.231-1035A>G		intron	N/A	ENSP00000269159.3
	IMPA2	ENST00000383376.9	TSL:1	n.*231+257A>G		intron	N/A	ENSP00000372867.4
	IMPA2	ENST00000588927.5	TSL:5	c.-337-1035A>G		intron	N/A	ENSP00000464767.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56596 AN: 151922 Hom.: 12910 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.373 AC: 56686 AN: 152042 Hom.: 12954 Cov.: 32 AF XY: 0.376 AC XY: 27948 AN XY: 74336

African (AFR) AF: 0.619 AC: 25663 AN: 41450

American (AMR) AF: 0.472 AC: 7202 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1062 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2439 AN: 5156

South Asian (SAS) AF: 0.239 AC: 1151 AN: 4824

European-Finnish (FIN) AF: 0.263 AC: 2780 AN: 10588

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15308 AN: 67976

Other (OTH) AF: 0.363 AC: 763 AN: 2104

Alfa AF: 0.274 Hom.: 8190

Bravo AF: 0.402

Asia WGS AF: 0.367 AC: 1279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.58
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3786285; hg19: chr18-12008847;